Regulation of signaling by wild-type and oncogenic Ras.

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Regulation of signaling by wild-type and oncogenic Ras. Regulation of signaling by wild-type and oncogenic Ras. Oncogenic Ras is constitutively GTP bound and regulates basal MAPK signaling. Growth factor receptors and negative regulatory proteins such as EGFR and EphA2, respectively, modulate wild-type Ras activity and in turn affect downstream signaling. In the basal state, wild-type Ras, which is predominantly GDP bound, inhibits oncogenic Ras signaling. Oncogenic Ras negatively regulates EGFR sensitivity. Suppression of basal MAPK signaling, via depletion of oncogenic Ras or pharmacologic inhibition of MEK, relieves this negative feedback and sensitizes cells to EGF stimulation. Amy Young et al. Cancer Discovery 2013;3:112-123 ©2013 by American Association for Cancer Research